Inhibition of Epithelial–Mesenchymal Transition and Migration in Cisplatin-resistant Cancer Through Combined Treatment With Cisplatin and SH003

Abstract

Background/Aim: This study investigated the synergistic effects of combining cisplatin and SH003 treatment on the viability, apoptosis, cytotoxicity, migration and epithelial–mesenchymal transition (EMT) in cisplatin-resistant cancer cell lines YD-8/CIS, YD-9/CIS and YD-38/CIS. Materials and Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess cell viability, while trypan blue exclusion assay was used to evaluate cytotoxicity. Flow cytometry and western blot analysis measured apoptotic cell death. Wound-healing assays evaluated cell migration and EMT markers. Combination index (CI) plots were used to evaluate the combinatory effects of the treatment. Results: Combination therapy significantly reduced cell viability more effectively than each agent alone, as demonstrated by the MTT assay, with CI plots confirming notable synergism. Trypan blue exclusion assays indicated increased cell death and cytotoxicity in combination treatment than in both monotherapies, although the increase was not significant. Flow cytometry and western blot analysis revealed no significant synergistic effect on apoptotic cell death. However, wound-healing assays revealed that the combination of cisplatin and SH003 significantly inhibited cell migration and regulated EMT markers, indicating the potential reversal of EMT. Conclusion: Combining cisplatin and SH003 therapy may potentially be a more effective strategy for treating cisplatin-resistant cancer by increasing cytotoxicity and inhibiting metastasis. Further research is required to elucidate the underlying mechanisms and evaluate the in vivo efficacy of this combination therapy.